Transformable peptide nanocarriers for expeditious drug release and effective cancer therapy via cancer-associated fibroblast activation

A novel cleavable amphiphilic peptide (CAP) was designed to be specifically responsive to fibroblast activation protein-α (FAP-α), a protease specifically expressed on the surface of cancer-associated fibroblasts. The CAP self-assembled into fiber-like nanostructures in solution, while the presence of hydrophobic chemotherapeutic drugs readily transformed the assemblies into drug-loaded spherical nanoparticles. The disassembly of these nanoparticles (CAP-NPs) upon FAP-α cleavage resulted in rapid and efficient release of the encapsulated drugs specifically at tumor sites. This Transformers-like drug delivery strategy could allow them to disrupt the stromal barrier and enhance local drug accumulation. Therapeutic results suggested that drug-loaded CAP-NPs hold promising tumor specificity and therapeutic efficacy for various solid tumor models, confirming its potential utility and versatility in antitumor therapy. A cleavable amphiphilic peptide (CAP) nanocarrier transforms from self-assembled nanofibers to spherical nanoparticles (NPs) by loading hydrophobic drugs, and cleavage by the tumor-specific protease, FAP-α, resulted in specific and efficient release of the encapsulated drugs at tumor sites. This Transformers-like drug nanocarrier could disrupt the stromal barrier, and enhance local drug accumulation.